Two strategies will be evaluated for potential vaccine generation utilizing the SIV/rhesus macaque animal model for AIDS. In the first strategy, we have generated novel viruses containing defined deletions in two conserved amino acid sequence motifs in the pol gene of SlV. These mutations were introduced into the proviral genome via recombinant polymerase chain reaction amplification. Studies performed to date demonstrate the recombinant viruses are non-infectious to both transformed human T-cells and rhesus macaque peripheral blood mononuclear cells. Further studies are planned to evaluate the ability of the recombinant viruses to bind and enter cells. If these novel viruses are found to enter cells, they will be further analyzed in rhesus macaques for generation of both cellular and humoral immune responses. Additionally, their pathogenic potential will be defined. The second strategy will involve the use of naked DNA as a vaccine. Plasmid constructs designed to express the gag and pol gene products of SIV will be generated and analyzed for antigen production. Constructs shown to express the gag antigens will be injected into rhesus macaques intramuscularly to evaluate the generation of a cellular immune response. An effective cellular immune response is believed to be required for vaccine generation. Animals exhibiting cellular and humoral immune responses from either strategy will be challenged with infectious SlVmac239 to evaluate the protective qualities of each. Infected animals will be closely evaluated for clinical disease progression, virus load, CD4/CD8 ratios, and immune response.